Studies conducted in our laboratory were designed to determine whether estrogen and progesterone regulate the humoral immune system. IgA and IgG were measured in blood and in uterine, vaginal, and salivary secretions in the rat at various stages of the reproductive cycle. These studies showed that at ovaluation (the time when estrogen levels in the blood are highest) rats had 5-12 fold higher levels of IgA and IgG in their uterine secretions than at any other stage of the reproductive cycle. In other studies, vaginal and salivary immunoglobulin results were just the opposite - levels were lowest at ovulation and elevated at all other times. We also observed that when estrogen is give to ovariectomized rats the changes that take place are the same as those that occur spontaneously during the reproductive cycle. Whereas short term estrogen administration enhances immunoglobulin levels in the uterus, long term treatment has an inhibitory effect on it. Similarly, when progesterone is given simultaneously with estrogen, it blocks the estrogen effect on IgA and IgG in the uterus and vagina. With the understanding that changes in the immune system do occur in response to estrogen and progesterone, our goal is now to understand just how the immune system is altered in response to these hormones.